The NYU Women's Health Study (NYUWHS) is a prospective cohort study of 14,274 healthy women who were enrolled in 1985-1991 at a breast cancer screening clinic in New York City. In addition to data on reproductive factors, medical history and lifestyle, the study collected serum samples from all participants at enrollment. Serum samples were also collected at subsequent breast cancer screening visits from over half the women. DNA is available for all study participants. To date, the NYUWHS has led to over 170 publications, 57 since 2010. The NYUWHS has initiated or participated in studies of cancer of the breast, endometrium, colorectum, ovary, lung, pancreas, kidney, liver and non-Hodgkin lymphoma (NHL). Exposures studied include diet, reproductive factors, and circulating levels of hormones, dietary markers, cytokines, and other biomarkers. The NYUWHS also participates in genome-wide association studies of pancreatic cancer, NHL, and glioma. Finally, the NYUWHS has been funded to conduct studies on cardiovascular disease and the NYUWHS data have motivated the development of new statistical methods. The objectives of this application are to maintain and enhance the infrastructure of the study. The specific aims are to: 1) continue cancer case ascertainment through both active and passive follow-up; 2) update exposure data, including diet and outdoor walking, through follow- up questionnaires; 3) collect tumor blocks for major cancer sites (breast, colorectal, endometrial, and lung) in order to assess risk factors according to molecular subtypes; 4) collect and validate data on neighborhood walkability. The continued follow-up is expected to identify an additional 1,389 cancer cases and the collection of tumor blocks will enhance the value of the study, as will the collection of data on neighborhood walkability. The NYUWHS has several specific strengths. First, serum collected at enrollment and DNA are available for all participants, making the biorepository a valuable resource to study associations between genetic variation, biomarkers, and disease risk. Second, repeat serum samples are available for over half of the participants and are very valuable to assess and improve temporal reliability of circulating markers. Third, while several large cancer cohorts started enrollment at age 50, 6,659 NYUWHS participants were <50 years of age at enrollment/blood donation, providing opportunities for the study of cancer risk factors among younger women. Finally, New York City is a particularly well-suited location for studies of walkability because there is a wide range in walkability across different neighborhoods.